Children with polyarticular-course juvenile idiopathic arthritis (? 5 joints; poly-JIA) often have refractory disease resulting in more joint damage, decreased quality of life, and worse functional outcomes compared to children with fewer joints. Treatment options now include multiple biologic agents with different mechanisms of action (tumor necrosis factor-? [TNF?], inhibition of T-cell co-stimulation, and interleukin-6). However the effectiveness of different classes of biologic medications in comparison to methotrexate (MTX) has not been evaluated in a single study. The proposed trial - Comparison of Methotrexate and Biologics in JIA (COMPARE-JIA) - will be the first trial to compare the effectiveness of different biologic therapies as initial therapy for poly-JIA, generating critical ata to guide treatment of children with early poly-JIA. The proposed trial will be conducted through the Childhood Arthritis and Rheumatology Research Alliance (CARRA), a network of over 300 pediatric rheumatologists in North America, and utilize existing CARRA Registry infrastructure (NIAMS RC2 AR058934) for data collection, site management, informatics, and the coordinating center (Duke Clinical Research Institute). The proposed trial will address the following specific aims: 1) Compare the effectiveness of 3 biologically distinct treatments (certolizumab, abatacept, and tocilizumab administered in combination with MTX) to MTX monotherapy, in achieving clinical inactive disease (CID) at 12 months in children with poly-JIA in the context of a randomized controlled trial; and 2) Compare the effectiveness of 3 biologically distinct treatments (certolizumab, abatacept, and tocilizumab administered in combination with MTX) to MTX monotherapy, in achieving CID at 6 months in children with poly-JIA. Trial innovations include use of the Juvenile Arthritis Disease Activity Score (a composite measure of disease activity) as an interim outcome and exploratory aims that include comparison of achievement of CID between the 3 biologic arms and analyses of clinical and biologic predictors of response and non-response at 12 months by analyzing individual patient trajectories. The specific aims for the planning phase are: 1) Solicit and incorporate stakeholder input into study design and protocol. The planning grant will support model recruitment and a meeting of study investigators, parent representative, and pharmaceutical company scientists to ensure study feasibility, community support, and relevant outcome measures; and 2) Finalize study design and operationalize study procedures. Final determination of study design and trial operations including study budget, protocol development, statistical analysis plan, manual of operating procedures, and informed consent forms will be accomplished during the planning period, culminating in the submission of a UM1 proposal for an innovative clinical trial that will demonstrate the comparative effectiveness of different classes of biologic agents as first-line therapy for poly-JIA and foster further study of JIA pathophysiology.